Quick question for you guys: When determining which reaction would follow from a 2° Carbon, it can go either Sn1 or Sn2, what would be the next best step to determine which it would be? If it has a good leaving group (a halide) would it be Sn2?

SN1 requires a good leaving group, because the leaving group has to leave without encouragement. SN2 needs a leaving group also, but a weaker (although still good) leaving group somewhat favors SN2.

More important factors are the solvent (with aprotic polar solvents favoring SN2 and polar protic solvents favoring SN1), and the size and properties of the nucleophile. Good nucleophiles favor SN2, while SN1 reactions will occur with essentially any nucleophile. Bulky nucleophiles, and especially bulky nucleophile that are strong bases favor elimination reactions rather than substitution reactions.

For most secondary substrates, unless all of the factors favor one reaction type, the products formed will be the result of more than one mechanism. For SN1 versus SN2 mechanism matters only if: 1) the carbocation intermediate is likely to rearrange, or 2) the substrate is chiral and stereocenter inversion is observable. (As it happens, products of SN1 reactions often exhibit more stereocenter inversion than complete stereocenter randomization.)

As an aside, this type of reaction chemistry is (in my opinion) one of the most important reasons why chemical engineers need to take organic chemistry. In most engineering courses, there is a "right" answer that may be calculated. In organic chemistry (and frequently in the real world), obtaining an answer requires balancing many qualitative factors, and performing experiments to arrive at an empirical observation is often necessary for a complete understanding of the system.

Hello guys, thought I'd chime in again to thank you for all the help and give you a mid-semester update.

I failed my first exam with a 59%. Tough to swallow since the teacher said well over 50% of the class got around the same grade, but she doesn't curve, so I really need to make this grade up on my next exam I have on Tuesday.

There isn't any one thing that is "difficult" in the traditional sense. And I think its this that is giving me the most difficulty. I have a good grasp of chirality (though I have to practice determining chirality and drawing enantiomers and diastereomers from newman projections) I can do chair confirmations fine, I understand what determines Sn1 and Sn2 reactions...but when it comes to applying this knowledge to a test and not messing up, I thoroughly have a hard time doing that.

Hey Pocky,

I know that feel, bro. I too just finished an exam, and got less than I wanted to get on it. I didn't fail, but it was much harder than it had a right to be, and since in my case plenty of other people got 100%, the fault lies entirely with me.

As they say in Starcraft II: Never give in, never surrender.

Also I wanted to say that I'll be attempting to learn OChem myself soon, as a personal project, and I have a feeling I'll be needing the Observatory's help. So keep up the good work and carry on.

Thanks for the encouraging words. I rock the shit out of lab work and doing lab reports, so if anything will allow me to pass, its this part of the class.

Polar Aprotic solvents (DMF, Acetone, DME, DMSO) all do not have a protonting hydrogen, but make a leaving group more "ready", for lack of a better term, to leave the substrate and allow the reaction to occur? Should I commit these solvents to memory?

Polar Aprotic solvents (DMF, Acetone, DME, DMSO) all do not have a protonting hydrogen, but make a leaving group more "ready", for lack of a better term, to leave the substrate and allow the reaction to occur? Should I commit these solvents to memory?

You should be aware of the effects of the solvents. The aprotic polar solvents seem to largely function by solubilizing the counterion of the nucleophile, while at the same time not stabilizing the nucleophile itself. This means that the nucleophile source material (e.g., potassium bromide) can be added to the solution and will dissolve, but the nucleophile will be more reactive, and therefore will cause the SN2 reaction to occur more readily. (This is especially true if if the leaving group is sufficiently insoluble as to precipitate from the solution, because this helps drives the reaction.)

Aprotic solvents have all of their hydrogens attached to weakly electronegative elements (especially carbon) instead of to more electronegative elements such as oxygen or nitrogen.

I am not a big fan of memorization, because there are too many organic compounds to make it feasible; instead, looking for mechanisms and general principles tends to be much more useful.

I fucked up on the latter part of the test where we were to piece together a molecule from IR, H-NMR and C-NMR. The IR had an Alcohol dip, A ketone and/or a conjugated ketone/C-C Double bond and I completely messed that part up. I have a hard time distinguishing the unique carbons. HDI was 5, so at least I got the ring part right, but other than that...

The rest of it I think I did okay on, I flew through the first part which was newman/fischer projections, SN1 and SN2 mechanisms and some IUPAC naming. Lets hope that I did well enough on the first part to not have the latter part tank me.

Polar Aprotic solvents (DMF, Acetone, DME, DMSO) all do not have a protonting hydrogen, but make a leaving group more "ready", for lack of a better term, to leave the substrate and allow the reaction to occur? Should I commit these solvents to memory?

You should be aware of the effects of the solvents. The aprotic polar solvents seem to largely function by solubilizing the counterion of the nucleophile, while at the same time not stabilizing the nucleophile itself. This means that the nucleophile source material (e.g., potassium bromide) can be added to the solution and will dissolve, but the nucleophile will be more reactive, and therefore will cause the SN2 reaction to occur more readily. (This is especially true if if the leaving group is sufficiently insoluble as to precipitate from the solution, because this helps drives the reaction.)

Aprotic solvents have all of their hydrogens attached to weakly electronegative elements (especially carbon) instead of to more electronegative elements such as oxygen or nitrogen.

I am not a big fan of memorization, because there are too many organic compounds to make it feasible; instead, looking for mechanisms and general principles tends to be much more useful.

Polar Aprotic solvents (DMF, Acetone, DME, DMSO) all do not have a protonting hydrogen, but make a leaving group more "ready", for lack of a better term, to leave the substrate and allow the reaction to occur? Should I commit these solvents to memory?

You should be aware of the effects of the solvents. The aprotic polar solvents seem to largely function by solubilizing the counterion of the nucleophile, while at the same time not stabilizing the nucleophile itself. This means that the nucleophile source material (e.g., potassium bromide) can be added to the solution and will dissolve, but the nucleophile will be more reactive, and therefore will cause the SN2 reaction to occur more readily. (This is especially true if if the leaving group is sufficiently insoluble as to precipitate from the solution, because this helps drives the reaction.)

Aprotic solvents have all of their hydrogens attached to weakly electronegative elements (especially carbon) instead of to more electronegative elements such as oxygen or nitrogen.

I am not a big fan of memorization, because there are too many organic compounds to make it feasible; instead, looking for mechanisms and general principles tends to be much more useful.

I hope this helps. Good luck with your studies!

In your example would the potassium then be a free floating ion or would it precipitate out along with the leaving group? Or do the spectator ions and leaving rarely form another product?

I've also come to the conclusion that O-Chem is harder than Physics. Physics is tangible is a very hands on way, even the electricity/magnetism.

O-Chem is a lot of visualizing in 3d space that is just not very conducive to thinking about things the same way you would do math or physics. Its a lot of imagining how things should look or react if you twist bonds around and break things apart.

Which is SHIT, because every teacher always says to use models, buy the model kit, but if you do so, you use that as a crutch to figure things out which fucks you in the end because come exam time, they sure as hell aren't handing out modeling kits.

And now I'm moving into E1 and E2 and Zaitsev and Hoffman products, which doesn't seem TOO complicated. The main thing I took away from lecture yesterday was that for E2 reactions, the hydrogens on the beta carbons need to be anti-periplanar to the leaving group.

Polar Aprotic solvents (DMF, Acetone, DME, DMSO) all do not have a protonting hydrogen, but make a leaving group more "ready", for lack of a better term, to leave the substrate and allow the reaction to occur? Should I commit these solvents to memory?

You should be aware of the effects of the solvents. The aprotic polar solvents seem to largely function by solubilizing the counterion of the nucleophile, while at the same time not stabilizing the nucleophile itself. This means that the nucleophile source material (e.g., potassium bromide) can be added to the solution and will dissolve, but the nucleophile will be more reactive, and therefore will cause the SN2 reaction to occur more readily. (This is especially true if if the leaving group is sufficiently insoluble as to precipitate from the solution, because this helps drives the reaction.)

Aprotic solvents have all of their hydrogens attached to weakly electronegative elements (especially carbon) instead of to more electronegative elements such as oxygen or nitrogen.

I am not a big fan of memorization, because there are too many organic compounds to make it feasible; instead, looking for mechanisms and general principles tends to be much more useful.

I hope this helps. Good luck with your studies!

In your example would the potassium then be a free floating ion or would it precipitate out along with the leaving group? Or do the spectator ions and leaving rarely form another product?

Depends on the charge of the leaving group. If its neutral you can't incorporate the potassium ion in the precipitate and maintain charge balance. There are a lot more charged leaving groups than neutral ones, and if these precipitate out then yes, they will take a spectator ion with them to maintain charge balance in the precipitate salt.

Polar Aprotic solvents (DMF, Acetone, DME, DMSO) all do not have a protonting hydrogen, but make a leaving group more "ready", for lack of a better term, to leave the substrate and allow the reaction to occur? Should I commit these solvents to memory?

You should be aware of the effects of the solvents. The aprotic polar solvents seem to largely function by solubilizing the counterion of the nucleophile, while at the same time not stabilizing the nucleophile itself. This means that the nucleophile source material (e.g., potassium bromide) can be added to the solution and will dissolve, but the nucleophile will be more reactive, and therefore will cause the SN2 reaction to occur more readily. (This is especially true if if the leaving group is sufficiently insoluble as to precipitate from the solution, because this helps drives the reaction.)

Aprotic solvents have all of their hydrogens attached to weakly electronegative elements (especially carbon) instead of to more electronegative elements such as oxygen or nitrogen.

I am not a big fan of memorization, because there are too many organic compounds to make it feasible; instead, looking for mechanisms and general principles tends to be much more useful.

I hope this helps. Good luck with your studies!

In your example would the potassium then be a free floating ion or would it precipitate out along with the leaving group? Or do the spectator ions and leaving rarely form another product?

Depends on the charge of the leaving group. If its neutral you can't incorporate the potassium ion in the precipitate and maintain charge balance. There are a lot more charged leaving groups than neutral ones, and if these precipitate out then yes, they will take a spectator ion with them to maintain charge balance in the precipitate salt.

If its a good leaving group, I'm assuming that it leaves with a charge, like a Halide or a Tosylate.

In your example would the potassium then be a free floating ion or would it precipitate out along with the leaving group? Or do the spectator ions and leaving rarely form another product?

As others have said, the precipitate needs to be neutral, so a negatively charged leaving group that precipitated (such as a halide) would have to precipitate with a potassium counterion. "Spectator" ions apply more to aqueous solutions, because water is (in general) much better at solubilizing ions than organic solvents.

I've also come to the conclusion that O-Chem is harder than Physics. Physics is tangible is a very hands on way, even the electricity/magnetism.

O-Chem is a lot of visualizing in 3d space that is just not very conducive to thinking about things the same way you would do math or physics. Its a lot of imagining how things should look or react if you twist bonds around and break things apart.

I am not sure that organic is harder than physics. It is different, and requires a different mental approach.

Quote:

Which is SHIT, because every teacher always says to use models, buy the model kit, but if you do so, you use that as a crutch to figure things out which fucks you in the end because come exam time, they sure as hell aren't handing out modeling kits.

I can't speak for your instructor. However, at my institution, we have model kits for check-out in the library, and I invite students to bring them to exams. Still, being able to visualize molecules in three dimensions can be much faster than building a model if you are time-constrained on an exam.

Quote:

And now I'm moving into E1 and E2 and Zaitsev and Hoffman products, which doesn't seem TOO complicated. The main thing I took away from lecture yesterday was that for E2 reactions, the hydrogens on the beta carbons need to be anti-periplanar to the leaving group.

I think?

In the E2 mechanism, the hydrogens and the leaving group need to be in the same plane to allow the developing p orbitals to overlap and form a pi bond. Anti-periplanar is more common than syn-periplanar, for the same reason that anti conformations are lower in energy than eclipsed conformations. However, in molecules that are locked into a planar structure, the leaving group and hydrogen can be on the same side of the system. (This does not work for cyclohexane systems, because in chair cyclohexane structures, the only periplanar atoms on adjacent carbons are in the axial positions, and the axial positions are anti to one another.

I've also come to the conclusion that O-Chem is harder than Physics. Physics is tangible is a very hands on way, even the electricity/magnetism.

O-Chem is a lot of visualizing in 3d space that is just not very conducive to thinking about things the same way you would do math or physics. Its a lot of imagining how things should look or react if you twist bonds around and break things apart.

I am not sure that organic is harder than physics. It is different, and requires a different mental approach.

Quote:

Which is SHIT, because every teacher always says to use models, buy the model kit, but if you do so, you use that as a crutch to figure things out which fucks you in the end because come exam time, they sure as hell aren't handing out modeling kits.

I can't speak for your instructor. However, at my institution, we have model kits for check-out in the library, and I invite students to bring them to exams. Still, being able to visualize molecules in three dimensions can be much faster than building a model if you are time-constrained on an exam.

Quote:

And now I'm moving into E1 and E2 and Zaitsev and Hoffman products, which doesn't seem TOO complicated. The main thing I took away from lecture yesterday was that for E2 reactions, the hydrogens on the beta carbons need to be anti-periplanar to the leaving group.

I think?

In the E2 mechanism, the hydrogens and the leaving group need to be in the same plane to allow the developing p orbitals to overlap and form a pi bond. Anti-periplanar is more common than syn-periplanar, for the same reason that anti conformations are lower in energy than eclipsed conformations. However, in molecules that are locked into a planar structure, the leaving group and hydrogen can be on the same side of the system. (This does not work for cyclohexane systems, because in chair cyclohexane structures, the only periplanar atoms on adjacent carbons are in the axial positions, and the axial positions are anti to one another.

Yeah, thats what I remember. Or should I say how I remember it.

I will kindly disagree about Physics, I can get A's and B's in Physics, so far, Organic Chemistry makes me feel like a drooling retard.

The good news is you shouldn't have to take biochemistry. I thought I had handle on organic, and the biochemistry showed me that I knew nothing. Or at least what I knew was only cute little tricks compared to what nature has done.

The good news is you shouldn't have to take biochemistry. I thought I had handle on organic, and the biochemistry showed me that I knew nothing. Or at least what I knew was only cute little tricks compared to what nature has done.

Was there anything specific in organic that gave you the most trouble?

So far, anything with reading IR, HNMR or CNMR can go to hell and die.

I'm trying to remember, but nothing particular comes to mind. I took organic while on academic probation (only 12 credits max) and working part time (third-shift at a convenience store) so I had a lot of time to spend studying my ass off. I actually liked IR and NMR problems since they kind of felt like a logic puzzle.

Most of my mistakes on exams came from trying to be too cute on synthesis problems where my professor would give us a starting molecule and a final molecule (and sometimes a list of available materials). I couldn't figure out a step and tries to approach it orthogonally, creating a synthesis that A) didn't work and B) confused my professor as to what i was trying to do, resulting in in partial credit. I would have been better off just drawing a question mark over the reaction arrow and continuing with the things I knew. Obviously, this is the kind of thing that changes from professor to professor.

So far, anything with reading IR, HNMR or CNMR can go to hell and die.

High five! /Borat

Dude, if it is any consolation I got a 22% on my organic chem II (cumulative with o-chem I) final and I made it through my chemE programs relatively unscathed (less orgo and spectroscopy). I think the only reason I passed spectroscopy was because they didn't want there again

Despite all that, I consider myself a pretty good chemical engineer. In the real world, there will be chemists who do this stuff leaving the details of making it work on a large scale to you.

Also, BuckG and Caillebotte, I think I learned more from your two posts than I did in the actual class!

In my class, day one of Orgo I, the professor gets up and states: "I don't like the fact that Chemical Engineers are in my class. I will teach this class to those of you who want to go on to get a PhD in synthetic organic chemistry" It never really went uphill from that point on.

So far, anything with reading IR, HNMR or CNMR can go to hell and die.

High five! /Borat

Dude, if it is any consolation I got a 22% on my organic chem II (cumulative with o-chem I) final and I made it through my chemE programs relatively unscathed (less orgo and spectroscopy). I think the only reason I passed spectroscopy was because they didn't want there again

Despite all that, I consider myself a pretty good chemical engineer. In the real world, there will be chemists who do this stuff leaving the details of making it work on a large scale to you.

Also, BuckG and Caillebotte, I think I learned more from your two posts than I did in the actual class!

In my class, day one of Orgo I, the professor gets up and states: "I don't like the fact that Chemical Engineers are in my class. I will teach this class to those of you who want to go on to get a PhD in synthetic organic chemistry" It never really went uphill from that point on.

The good news is you shouldn't have to take biochemistry. I thought I had handle on organic, and the biochemistry showed me that I knew nothing. Or at least what I knew was only cute little tricks compared to what nature has done.

The midterm and final exams I sat for medical biochemistry were hands down the toughest two exams I've ever taken.

That being said, I still much prefer biochemistry to organic.

zeotherm wrote:

In my class, day one of Orgo I, the professor gets up and states: "I don't like the fact that Chemical Engineers are in my class. I will teach this class to those of you who want to go on to get a PhD in synthetic organic chemistry" It never really went uphill from that point on.

In my class, day one of Orgo I, the professor gets up and states: "I don't like the fact that Chemical Engineers are in my class. I will teach this class to those of you who want to go on to get a PhD in synthetic organic chemistry" It never really went uphill from that point on.

Imagine how all of the pre-meds felt

At my undergrad, there were two different organic chemistry classes. The one for the Chemistry and Chemical Engineering majors, then the one for everybody else. I think pre-meds would have passed out in our Orgo class.

In my class, day one of Orgo I, the professor gets up and states: "I don't like the fact that Chemical Engineers are in my class. I will teach this class to those of you who want to go on to get a PhD in synthetic organic chemistry" It never really went uphill from that point on.

Imagine how all of the pre-meds felt

At my undergrad, there were two different organic chemistry classes. The one for the Chemistry and Chemical Engineering majors, then the one for everybody else. I think pre-meds would have passed out in our Orgo class.

I'm curious as to what the differences were. I mean, the information and mechanisms are all the same, I'm going to assume the "other" class was easier or less detailed? What was left out?

Today I'm doing homework for Chapter 8 which is E1 and E2 reactions, with some Sn1 and Sn2 stuff thrown in and we have to decide which path it would take. Not too difficult (bulky reagents favor E2, if there is heat applied, more than likely E1).

Today I'm doing homework for Chapter 8 which is E1 and E2 reactions, with some Sn1 and Sn2 stuff thrown in and we have to decide which path it would take. Not too difficult (bulky reagents favor E2, if there is heat applied, more than likely E1).

Careful. E2 requires a strong base; E1 does not. Heating an E2-capable reaction mixture makes E2 more likely also (in part as the result of entropic effects).

Generally, E2 and SN2 compete for primary (usually favors SN2, unless the strong base is too bulky to be a good nucleophile) and secondary substrates (usually favors E2, if the nucleophile is a strong base).

Other than dehydration reactions, E1 is a bit difficult to accomplish, because the presence of any nucleophile will allow SN1 to dominate. Also, the real reason why you need to recognize both SN1 and E1 is that they proceed through a carbocation intermediate, which is prone to rearrangement.

I'm curious as to what the differences were. I mean, the information and mechanisms are all the same, I'm going to assume the "other" class was easier or less detailed? What was left out?

No idea. Back when I was pre-med everyone taking organic was thrown into the same 500 seat lecture hall regardless of major. Lambs to the slaughter...

Pre-meds have to take organic for two reasons, one of which is good, and one of which is bad.

The good reason is that organic chemistry is useful to physicians. Although not all physicians will admit it, understanding biochemistry requires understanding organic chemistry, and the thought processes developed in a properly taught organic chemistry course are also useful in dealing with multivariable qualitative problems of any sort. Unfortunately, some medical schools are considering dropping organic as a requirement for admission; the end result is that the physicians will have a much poorer understanding of the underlying causes of the diseases that they will be treating.

The bad reason is that organic chemistry is perceived to be a difficult course, and it weeds out some potential medical school applicants. (This role in the medical school admissions process is probably why some medical schools are considering dropping organic requirements.)

The "lambs to the slaughter" is in part because many people considering medicine as a career are unprepared for the mental demands. It is also, again, based on the wide-spread perception that organic chemistry is especially difficult, and is part of the reason that pre-meds are frequently advised to major in biology rather than chemistry. (Chemistry and physics majors usually have an "easier" time with the medical school curriculum, at least at the institutions with which I was associated.)

Today I'm doing homework for Chapter 8 which is E1 and E2 reactions, with some Sn1 and Sn2 stuff thrown in and we have to decide which path it would take. Not too difficult (bulky reagents favor E2, if there is heat applied, more than likely E1).

Careful. E2 requires a strong base; E1 does not. Heating an E2-capable reaction mixture makes E2 more likely also (in part as the result of entropic effects).

Generally, E2 and SN2 compete for primary (usually favors SN2, unless the strong base is too bulky to be a good nucleophile) and secondary substrates (usually favors E2, if the nucleophile is a strong base).

Other than dehydration reactions, E1 is a bit difficult to accomplish, because the presence of any nucleophile will allow SN1 to dominate. Also, the real reason why you need to recognize both SN1 and E1 is that they proceed through a carbocation intermediate, which is prone to rearrangement.

The carbocation arrangement is drilled into my memory. I couldn't forget that even if I tried. The example our prof used most is TBuOK for E2 reactions since it is so big that SN2 is highly unlikely.

So if I see strong base, more likely than not it'll favor E2, if I see a weak base but heat, it is E1?

The good reason is that organic chemistry is useful to physicians. Although not all physicians will admit it, understanding biochemistry requires understanding organic chemistry.... Unfortunately, some medical schools are considering dropping organic as a requirement for admission; the end result is that the physicians will have a much poorer understanding of the underlying causes of the diseases that they will be treating.

Disagree. In my personal opinion, organic chemistry is about 20-25 percent useful at MOST to understanding medical biochemistry. And even the value of much of the medical biochemistry curriculum is debatable. Useful biochem aside and absolutely no offense intended, it's plain silly to say that organic chemistry has really ANY influence on a physician's understanding of pathophysiology, let alone that a deficiency in o-chem knowledge will cause their comprehension to be "much poorer." For examples look no further than the discussions transpiring on this thread... E1 mechanisms, polar aprotic solvents, good leaving groups - these things don't play a role in clinical practice. I'm not going to say it's NEVER useful, but examining a patient using an organic chemistry based approach really isn't going to get you anything meaningful.

If you can skip organic and understand well enough what's going on in biochem, you've lost nothing. Even a lot of biochem steps out of scope. Example - In biochem you learn about the chemical makeup, bond angles and steric strain of the porphyrin ring of Heme, how ferrous iron can bind one O2, and so forth. Not relevant to clinical medicine. On the other hand, for physiology (a MUCH more clinically relevant course) my professor put up a diagram of hemoglobin (heme in green) and began by saying something like, "this is hemoglobin. For the purposes of physiology, you need to know that there are four green things, and each green thing binds an O2."

Caillebotte wrote:

The "lambs to the slaughter" is in part because many people considering medicine as a career are unprepared for the mental demands.

Totally agree. In lots of med programs (mine included) by the time you get to basic sciences graduation day you've lost half of your class due to drop outs or the need to repeat a course. An undergraduate organic chemistry course somewhat resembles the type of academic challenge one will encounter in a medical program - though the difficulty is increased proportionately.

Sorry if I come off a bit overzealous. I'll admit to being fanatical about this subject because I sat through four years of undergrad that was tantamount to jumping through hoops. I recognize it was necessary in some respects to thin the herd, but that doesn't mean it wasn't a miserable experience.

So if I see strong base, more likely than not it'll favor E2, if I see a weak base but heat, it is E1?

Strong bases are usually good nucleophiles, so strong base implies E2 or SN2, with the reaction mechanism that dominates depending on other factors (especially substrate structure).

E1 is usually the last resort, and is fairly rare for most substrates. The exception is that E1 dominates for dehydration reactions, in which a strong acid (sulfuric or phosphoric acid) is added to an alcohol. The strong acid protonates the alcohol, yielding water and a carbocation. If the strong acid is also a poor nucleophile (like HSO4- or H2PO4-), then dehydration to an alkene is the only route to an immediate non-alcohol product. (Attack on the carbocation by water, which will be present, merely gives an alcohol.) Because dehydration reactions are normally distilled as the reaction proceeds, and because the alkene has a lower boiling point than the alcohol, it is usually possible to generate the alkene as the major product. For non-alcohol substrates, the leaving group has to be a very good one and the substrate must be able to form a "stable" carbocation, with no other nucleophile present in the reaction to yield appreciable amounts of E1 product; if any nucleophile is present, the main product will be SN1 for these conditions.

Disagree. In my personal opinion, organic chemistry is about 20-25 percent useful at MOST to understanding medical biochemistry.

Basically, you are saying that you can learn thermodynamics, kinetics, reaction mechanisms, properties of organic molecules, and the forces involved in protein folding and membrane formation in other courses. In principle, this is true, but these are major topics in organic chemistry.

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And even the value of much of the medical biochemistry curriculum is debatable. Useful biochem aside and absolutely no offense intended, it's plain silly to say that organic chemistry has really ANY influence on a physician's understanding of pathophysiology, let alone that a deficiency in o-chem knowledge will cause their comprehension to be "much poorer." For examples look no further than the discussions transpiring on this thread... E1 mechanisms, polar aprotic solvents, good leaving groups - these things don't play a role in clinical practice. I'm not going to say it's NEVER useful, but examining a patient using an organic chemistry based approach really isn't going to get you anything meaningful.

You have not really been following the underlying point. The point is not the details, although an understanding of the role of leaving groups in reactions is important in a wide variety of pathophysiological and pharmacological processes. The real point is the thought processes: being able to deal with problems where more than one answer is correct, and where it is necessary to make assessments in the absence of complete quantitative data.

Quote:

If you can skip organic and understand well enough what's going on in biochem, you've lost nothing. Even a lot of biochem steps out of scope. Example - In biochem you learn about the chemical makeup, bond angles and steric strain of the porphyrin ring of Heme, how ferrous iron can bind one O2, and so forth. Not relevant to clinical medicine.

Of course, assuming that the process of clinical medicine is entirely a trade. If the clinician is a mechanic, then the clinician does not have to understand the underlying mechanism. However, if the clinician is treating a hemoglobinopathy (to use an example dependent on heme oxygen binding), the clinician must either understand the underlying mechanisms or rely totally on methods developed by someone who does. Since those methods may not apply to all patients, the ignorant clinician you seem to be favoring may not be providing the best care for the patient.

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On the other hand, for physiology (a MUCH more clinically relevant course) my professor put up a diagram of hemoglobin (heme in green) and began by saying something like, "this is hemoglobin. For the purposes of physiology, you need to know that there are four green things, and each green thing binds an O2."

Which obviously explains the problems that occur in HbS mutations!

How does high altitude affect the "four green things" and when does this matter? You are describing physiology as a branch of mechanical engineering. While it is possible to ignore the underlying mechanisms, and memorize treatments that might apply, the result is frequently suboptimal, and provides no method for dealing with memory lapses.

Caillebotte wrote:

The "lambs to the slaughter" is in part because many people considering medicine as a career are unprepared for the mental demands.

Quote:

Totally agree. In lots of med programs (mine included) by the time you get to basic sciences graduation day you've lost half of your class due to drop outs or the need to repeat a course. An undergraduate organic chemistry course somewhat resembles the type of academic challenge one will encounter in a medical program - though the difficulty is increased proportionately.

Sorry if I come off a bit overzealous. I'll admit to being fanatical about this subject because I sat through four years of undergrad that was tantamount to jumping through hoops. I recognize it was necessary in some respects to thin the herd, but that doesn't mean it wasn't a miserable experience.

It sounds as though you made a poor choice in selecting an undergraduate institution, and probably had a poor organic chemistry course.

And having dealt with a lot of medical students; most of the ones who had trouble with the basic science courses made me want to take the advice of a friend, and have tattooed on my chest "Not to be opened by a graduate of <insert medical school>".

Many physicians have a tendency to underrate the importance of understanding the basic sciences. Their failure to understand how to evaluate new information discovered after graduation, and their failures of memorization due to lack of understanding of the relevant mechanisms frequently results in adverse effects on their patients.

Is the distinction between a strong base and a good nucleophile just based on what the reagent attacks? Base will attack a hydrogen, a nucleophile will attack a Carbon?

That would be one way of describing it; in most cases, it helps to look at the reasons underlying the observation.

Strong bases are relatively unstable species, usually because they are conjugate bases of stable molecules. So, water is stable; hydroxide is a fairly strong base. Ammonia is a stable molecule; the NH2(-) ion is a very strong base. Acetic acid is stable, but is a weak acid, because of resonance stabilization in the conjugate base, so acetate is a relatively weak base. Chloride, bromide, and iodide ions are rather stable species, and are extremely weak bases, but rather good nucleophiles.

If an acid has a large pKa, the conjugate base will be a strong base. Ammonia has a pKa of about 38, water has a pKa of 15.7, and acetic acid 4.76. For the halogens, the pKa values of HCl, HBr, and HI are a bit difficult to measure, but are generally considered to be -7 or more negative, so the halides are seriously weak bases.

Strong bases are good nucleophiles because they are unstable and therefore reactive. They tend to react readily with hydrogens (both because there are usually several hydrogens, and because reaching the carbon is often more difficult for steric reasons). They won't abstract hydrogens from positions that are not beta to a leaving group because the resulting carbanion is likely to be more unstable than the strong base.

For all reactions, if you look at the reactants and the possible products and can evaluate which will be more stable, it is often possible to predict reactions outcomes. (Often, if you understand what helps to stabilize the various species and still cannot decide which is more stable, the outcome is likely to be a mixture of products.)

For secondary substrates, the alkene will be more substituted, and therefore more stable, which is part of the reason that strong bases are more likely to react via E2 than SN2 for secondary substrates.

Basically, you are saying that you can learn thermodynamics, kinetics, reaction mechanisms, properties of organic molecules, and the forces involved in protein folding and membrane formation in other courses. In principle, this is true, but these are major topics in organic chemistry.

Yeah, you can surmise the points that are relevant from biochem. Biochem was the first time bioenergetics ever made sense to me (as well as pKa's and amino acid acid-base dissociation curves!) Also, what you've mentioned were not "major" topics of my o-chem education by any stretch. It was a few years ago now but I think I spent 90% of the time trying to figure out which nitrogen is more basic, or something. Or getting compound A to look like compound B twelve steps later.

Caillebotte wrote:

You have not really been following the underlying point. The point is not the details, although an understanding of the role of leaving groups in reactions is important in a wide variety of pathophysiological and pharmacological processes. The real point is the thought processes: being able to deal with problems where more than one answer is correct, and where it is necessary to make assessments in the absence of complete quantitative data.

Understanding the role and letting those concepts guide your treatment is one thing. It's enormously different from sitting at a white board debating whether drug A or drug B is better for the patient because Drug A has a more basic nitrogen at the 17 position but drug B shows resonance. That's for chemists and that conversation is just never going to occur between clinicians. That said, you're absolutely right, there are always multiple correct answers but it's important to learn how to choose the "best" answer. You say the point is not in the details, and I agree with you, but too often does this become the focus.

Caillebotte wrote:

Of course, assuming that the process of clinical medicine is entirely a trade. If the clinician is a mechanic, then the clinician does not have to understand the underlying mechanism. However, if the clinician is treating a hemoglobinopathy (to use an example dependent on heme oxygen binding), the clinician must either understand the underlying mechanisms or rely totally on methods developed by someone who does. Since those methods may not apply to all patients, the ignorant clinician you seem to be favoring may not be providing the best care for the patient.

Again understanding and approach are two different things. One should absolutely understand the molecular mechanisms at play so one can visualize what's happening. Perhaps I chose a poor example with hemoglobin because in this case molecular interactions actually are immediately relevant to treatment. But when attempting to oxygenate a patient in severe distress, you're not going to be recalling bond angles, that's just not a useful approach. Your clinician who's standing there thinking about steric hindrance and polar aprotic solvents instead of bagging the patient isn't exactly at the top of his game either.

Let's be realistic, I think we can agree there's an appropriate middleground.

Caillebotte wrote:

Which obviously explains the problems that occur in HbS mutations!

How does high altitude affect the "four green things" and when does this matter? You are describing physiology as a branch of mechanical engineering. While it is possible to ignore the underlying mechanisms, and memorize treatments that might apply, the result is frequently suboptimal, and provides no method for dealing with memory lapses.

Somewhere between too much and too little, there is a happy medium in terms of level of detail. There is no "bad" knowledge - it's never going to hurt you to know more about something. You also can't possibly know everything. You're never going to remember every concept. You need to focus on what's most relevant, and for the case of clinical medical practice, an undergraduate organic chemistry course falls outside those bounds 99% of the time. In your sickle cell example you have to admit that somewhere around the transition from biochemistry to organic chemistry, you reach the limit of what is still clinically relevant.

There is an art to the unique combination of scientific knowledge and understanding that goes into medical practice. Do you truly feel that skipping organic chem in undergrad, given a strong comprehension of biochemistry, would make doctors' understanding of their patients' ailments "much poorer?" That the level of proficiency among physicians in this country would fall dramatically due to a flagrant lack of mastery of undergraduate organic chemistry? Would people pour out of hospitals in droves, terrified at the prospect of being cared for by physicians with no working knowledge of infrared spectroscopy? Would they then take to the streets en masse, looting and rioting and decrying Western medicine? Maybe the Mayans were right - it's still only November.

Caillebotte wrote:

It sounds as though you made a poor choice in selecting an undergraduate institution, and probably had a poor organic chemistry course.

My undergraduate institution was and is considered reputable. To say I was dissatisfied with the quality of instruction is a gross understatement. Most people I know express similar sentiments regarding their own undergraduate experiences.

Won't argue with you on the quality of the organic chemistry course.

Caillebotte wrote:

And having dealt with a lot of medical students; most of the ones who had trouble with the basic science courses made me want to take the advice of a friend, and have tattooed on my chest "Not to be opened by a graduate of <insert medical school>".

Many physicians have a tendency to underrate the importance of understanding the basic sciences. Their failure to understand how to evaluate new information discovered after graduation, and their failures of memorization due to lack of understanding of the relevant mechanisms frequently results in adverse effects on their patients.

If I sound as though I don't value the basic medical sciences then I'm afraid I've given you the wrong impression. The basic medical sciences are pretty much the entire foundation of Western medicine. On top of that, they're fascinating. I think you said it perfectly - physicians need to be fluent in the "relevant mechanisms."

Ethoxide is a good nucleophile, being a primary anion with no steric hindrance. Isopropoxide is a stronger base but less nucleophilic, the methyl groups hindering a SN2 approach. t-Butoxide is a very strong base but a very poor nucleophile.

The more steric hindrance, the more likely the reaction is to proceed by SN1 and/or E1

Same with the substrate being attacked. If there are groups other than hydrogen(or a fluoride), such as a methyl or phenyl, then the SN2 reaction is more difficult. beta-branching makes SN2 really difficult.

So with a bulky base and/or a hindered reactive site, consider SN1 or E1. A carbocation is formed. Is it stable as is or will it be at a lower energy state if it rearranges?

Bulky bases also good for E2 since they can grab a proton but not displace a leaving group. (yes there are exceptions but not in sophomore organic. ) but in the absence of a leaving group, it will be SN1 or E1.

If I sound as though I don't value the basic medical sciences then I'm afraid I've given you the wrong impression. The basic medical sciences are pretty much the entire foundation of Western medicine. On top of that, they're fascinating. I think you said it perfectly - physicians need to be fluent in the "relevant mechanisms."

I would say basic science is the foundation of Western medicine. Most physicians don't use any physics in their daily practice, and what they need could be learned in physiology. Most don't use calculus. Most don't use organic chemistry.

But those subjects are the foundation of science. They make the whole thing come together in molecular biology and biochemistry. I would add that good introductory semesters in classical zoology, botany and microbiology would round out the education, being the pinnacle of biochemistry and molecular biology.

Ethoxide is a good nucleophile, being a primary anion with no steric hindrance. Isopropoxide is a stronger base but less nucleophilic, the methyl groups hindering a SN2 approach. t-Butoxide is a very strong base but a very poor nucleophile.

The more steric hindrance, the more likely the reaction is to proceed by SN1 and/or E1

Same with the substrate being attacked. If there are groups other than hydrogen(or a fluoride), such as a methyl or phenyl, then the SN2 reaction is more difficult. beta-branching makes SN2 really difficult.

So with a bulky base and/or a hindered reactive site, consider SN1 or E1. A carbocation is formed. Is it stable as is or will it be at a lower energy state if it rearranges?

Bulky bases also good for E2 since they can grab a proton but not displace a leaving group. (yes there are exceptions but not in sophomore organic. ) but in the absence of a leaving group, it will be SN1 or E1.

Something else I've also drilled into my head. Steric hindrance is a good factor to judge what mechanism will happen, hence my teachers apparently love affair with using TBuOK in her examples.

As I was doing my homework last night, I was reviewing the practice mechanisms and seem to notice if there is an OH in the substrate, and a strong acid as the reagent, my mind automatically switches over to E1/Sn1. Is this good or bad? The way I see it is that the OH is a shitty leaving group, but it can grab, say, an H from H2SO4, then that readily leaves, and then the mechanism continues. More than one step leads me to E1/Sn1.

As I was doing my homework last night, I was reviewing the practice mechanisms and seem to notice if there is an OH in the substrate, and a strong acid as the reagent, my mind automatically switches over to E1/Sn1. Is this good or bad? The way I see it is that the OH is a shitty leaving group, but it can grab, say, an H from H2SO4, then that readily leaves, and then the mechanism continues. More than one step leads me to E1/Sn1.

Yes, that is right. In fact, congratulations! Many of my students fixate on E2 for performing eliminations; with alcohols, they want to add a strong base, and forget that: 1) hydroxide is poor leaving group, and more importantly, 2) strong bases deprotonate alcohols, whether you want them to or not. (Some try to get around this by proposing addition of a strong acid and then a strong base in quick succession; I tell them that this is only possible in enzyme active sites.) For alcohols, strong (Bronsted-Lowry) acids create a good leaving group; the rest of the reaction depends on the counterion for the proton, with sulfuric or phosphoric acid yielding alkenes, and HCl, HBr, and HI giving SN1 reactions. (Either way, the reaction has a carbocation intermediate, so rearrangements are an issue.)